Oral delivery of pH-sensitive nanoparticles loaded Celastrol targeting the inflammatory colons to treat ulcerative colitis.

IF 6.7 1区 工程技术 Q1 CELL & TISSUE ENGINEERING Journal of Tissue Engineering Pub Date : 2024-08-10 eCollection Date: 2024-01-01 DOI:10.1177/20417314241265892
Yue Zhao, Yinlian Yao, Shilong Fan, Xin Shen, Xingxing Chai, Zimin Li, Jiachun Zeng, Jiang Pi, Zhikun Zhou, Gonghua Huang, Hua Jin
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Abstract

The incidence of ulcerative colitis (UC) is rapidly rising worldwide. Oral drug delivery system is a promising approach for treating UC, but it often fails to accumulate to the inflammatory lesions, thus, it is impressive to develop a colon-targeted oral delivery system for preventing systemic toxicity and maintaining UC therapeutics. Here, a negative-charged PLGA nanoparticle system was designed to encapsulate celastrol (Cel), and then chitosan and mannose were coated on the surface of the nanoparticles (MC@Cel-NPs) to endow these nanoparticles with the mucosal adsorption and macrophage targeting abilities. MC@Cel-NPs demonstrate excellent resist decomposition ability against the strong acidic gastrointestinal environment, and accumulates in the specific inflammatory sites through the affinity of electrostatic reaction. After releasing the payload, MC@Cel-NPs could remarkably alleviate the colon inflammation, which was evidenced by the decrease in pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in both blood and colon sections, and scavenging reactive oxygen species (ROS) in colon cells, including macrophage, neutrophil, T cell, and B cell. This nanoparticle system provided a new approach for treating UC through a Chinese herbal ingredient-related oral delivery manner.

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以炎症性结肠为靶点,口服含 Celastrol 的 pH 值敏感纳米颗粒,治疗溃疡性结肠炎。
溃疡性结肠炎(UC)的发病率在全球迅速上升。口服给药系统是治疗溃疡性结肠炎的一种很有前景的方法,但它往往不能在炎症病变部位蓄积,因此,开发一种结肠靶向口服给药系统以防止全身毒性并维持溃疡性结肠炎的治疗效果令人印象深刻。本文设计了一种带负电荷的PLGA纳米颗粒系统来包裹西司他醇(Cel),然后在纳米颗粒(MC@Cel-NPs)表面包覆壳聚糖和甘露糖,使这些纳米颗粒具有粘膜吸附和巨噬细胞靶向能力。MC@Cel-NPs 在强酸性胃肠道环境中表现出优异的抗分解能力,并通过静电反应的亲和力在特定炎症部位聚集。释放有效载荷后,MC@Cel-NPs 能显著缓解结肠炎症,这表现在血液和结肠切片中的促炎细胞因子 TNF-α、IL-1β 和 IL-6 均有所下降,并能清除结肠细胞(包括巨噬细胞、中性粒细胞、T 细胞和 B 细胞)中的活性氧(ROS)。这种纳米颗粒系统通过与中药成分相关的口服给药方式为治疗 UC 提供了一种新方法。
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来源期刊
Journal of Tissue Engineering
Journal of Tissue Engineering Engineering-Biomedical Engineering
CiteScore
11.60
自引率
4.90%
发文量
52
审稿时长
12 weeks
期刊介绍: The Journal of Tissue Engineering (JTE) is a peer-reviewed, open-access journal dedicated to scientific research in the field of tissue engineering and its clinical applications. Our journal encompasses a wide range of interests, from the fundamental aspects of stem cells and progenitor cells, including their expansion to viable numbers, to an in-depth understanding of their differentiation processes. Join us in exploring the latest advancements in tissue engineering and its clinical translation.
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